Dairy cattle of different ages experience different living conditions and varied frequency of antibiotic administration that likely influence the distribution of microbiome and resistome in ways that reflect different risks of microbial transmission. To assess the degree of variance in these distributions, fecal and soil samples were collected from six distinct housing areas on commercial dairy farms (n = 7) in Washington State. 16S rRNA gene sequencing indicated that the microbiota differed between different on-farm locations in feces and soil, and in both cases, the microbiota of dairy calves was often distinct from others (P < 0.05). Thirty-two specific antibiotic resistance genes (ARGs) were widely distributed on dairies, of which several clinically relevant ARGs (including cfr, cfrB, and optrA) were identified for the first time at U.S. dairies. Overall, ARGs were observed more frequently in feces and soil from dairy calves and heifers than from hospital, fresh, lactation and dry pens. Droplet-digital PCR demonstrated that the absolute abundance of floR varied greatly across housing areas and this gene was enriched the most in calves and heifers. Furthermore, in an extended analysis with 14 dairies, environmental soils in calf pens had the most antibiotic-resistant Escherichia coli followed by heifer and hospital pens. All soil E. coli isolates (n = 1,905) are resistant to at least 4 different antibiotics, and the PFGE analysis indicated that florfenicol-resistant E. coli is probably shared across geographically-separated farms. This study identified a discrete but predictable distribution of antibiotic resistance genes and organisms, which is important for designing mitigation for higher risk areas on dairy farms.

Parabens, broad-spectrum antimicrobial preservatives widely used in various consumer products and food, are suspected to be linked with several adverse health effects in humans, especially newborn babies, infants, and young children. While human exposure to parabens has been frequently reported by measuring the concentration of parabens in urine, similar measurements in breast milk have rarely been made. To determine paraben concentrations in breast milk and possible sources of exposure, four major parabens, including methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP) were measured in breast milk samples collected from 260 lactating women in South Korea. Demographic, socioeconomic, and behavioral factors associated with the presence of parabens in breast milk were determined. EP concentrations were detected at the highest levels in breast milk samples, followed by MP, PP, and BP. Pre-pregnancy BMI, parity, use of basic skin care products, use of cosmetics, canned beverage, and type of milk consumption were associated with higher frequencies of paraben detection. In addition, type of milk, parity, and drinking status were significantly associated with the concentration of EP. Multiple regression analyses showed that colostrum and transitional milk samples had higher levels of EP than mature milk samples. The estimated daily intake of parabens in infants via breastfeeding appears to be negligible when compared to the acceptable daily intake values set forth by the European Food Safety Authority (EFSA); however, considering the vulnerability of breastfed infants and ubiquitous sources of exposure from daily use of household and personal toiletries, efforts to identify sources and mitigate exposure are warranted.

We studied neurodevelopment in infants from two communities. Children living in the vicinity of tin-ore kilns and smelters – TOKS; n = 51) were compared to children from a fishing village (Itapuã; n = 45). Mean hair-Hg (HHg) concentrations were significantly higher in Itapuã children which received significantly (p = 0.0000001) less mean ethylmercury (88.6 μg) from Thimerosal-containing vaccines (TCV) than the TOKS children (120 μg). Breast-milk Pb concentrations were significantly higher in the TOKS mothers (p = 0.000017; 10.04 vs. 3.9 μg L−1). Bayley mental development index (MDI) and psychomotor development index (PDI) were statistically significant (respectively p < 0.0000001, p = 0.000007) lower for the TOKS children only at 24 months of age. Multivariate regression analysis showed that MDI was negatively affected by breast-milk Pb and by HHg. PDI was positively affected by breastfeeding and negatively affected by ethylmercury. Milestone achievements were negatively affected by breast-milk Pb (age of walking) and by HHg (age of talking).

Polybrominated diphenyl ethers (PBDEs) are flame retardants and the congener 2, 2′, 4, 4′-tetrabromodiphenyl ether (PBDE-47) is capable of inducing thyroid endocrine disruption and developmental toxicity. However, little is known about whether developmental PBDE-47 exposure-elicited alterations in semen quality is associated with thyroid hormones (THs) perturbation. In this research, we sought to explore the impacts of gestational and lactational PBDE-47 exposure on adult sperm quantity and motility, and its link with THs levels. For this purpose, female Sprague-Dawley rats were administered environmentally relevant PBDE-47 levels (0.1, 1.0, 10 mg/kg/day) by oral gavage from prepregnancy through lactation cessation to achieve early-life exposure of offspring and to mimic the actual exposure. Sperm quantity and motility together with serum THs levels from male offspring were determined on postnatal day 88. In utero and lactational exposure to PBDE-47 boosted the weight gain while reduced the relative testis weight in adult male offspring. These were accompanied with the reductions in sperm counts (total and living sperm counts), the percentage of progressive sperm motility, sperm velocities (curvilinear velocity, straight-line velocity and average path velocity), motion path (beat cross frequency, linearity and wobble) and linear motile sperm parameters (count, motility and concentration). Further studies identified that the levels of serum triiodothyronine (T₃) were increased by PBDE-47 exposure and negatively associated with those differential semen parameters on quantity and motility. Collectively, our results indicate that exposure to low-level PBDE-47 during early-life development impairs semen quality in adult rats, which could be mediated partially by abnormal T₃ levels.

Epidemiological indications connect maternal and developmental presence or exposure to pesticides with an increased risk for a spectrum of neurological trajectories. To provide pre-clinical data in support of this hypothesis, we used two distinct experimental models. First, female and male mice were fed immediately prior to mating, and the resulting pregnant dams were continously fed during gestation and lactation periods using chow pellets containing a cocktail of six pesticides at tolerable daily intake levels. Male and female offspring were then tracked for behavioral and in vivo electrophysiological adaptations. Second, a zebrafish model allowed us to screen toxicity and motor-behavior outcomes specifically associated with the developmental exposure to a low-to-high concentration range of the cocktail and of each individual pesticide. Here, we report anxiety-like behavior in aging male mice maternally exposed to the cocktail, as compared to age and gender matched sham animals. In parallel, in vivo electrocorticography revealed a decrease in gamma (40–80 Hz) and an increase of theta (6–9 Hz) waves, delineating a long-term, age-dependent, neuronal slowing. Neurological changes were not accompanied by brain structural malformations. Next, by using zebrafish larvae, we showed an increase of all motor-behavioral parameters resulting from the developmental exposure to 10 μg/L of pesticide cocktail, an outcome that was not associated with midbrain structural or neurovascular modifications as assessed by in vivo 2-photon microscopy. When screening each pesticide, chlorpyrifos elicited modifications of swimming parameters at 0.1 μg/L, while other components provoked changes from 0.5 μg/L. Ziram was the single most toxic component inducing developmental malformations and mortality at 10 μg/L. Although we have employed non-equivalent modalities and timing of exposure in two dissimilar experimental models, these outcomes indicate that presence of a pesticide cocktail during perinatal periods represents an element promoting behavioral and neurophysiological modifications. The study limitations and the possible pertinence of our findings to ecotoxicology and public health are critically discussed.

Acrylamide is a well-known carcinogen and neurotoxic substance that has been discovered in frying or baking carbohydrate-rich foods and is widely found in soils and groundwater. The purpose of this study was to investigate the adverse effects of exposure to acrylamide on skeletal development. After treatment with acrylamide in zebrafish embryos, the survival and hatching rates decreased, and the body length shortened, with cartilage malformation and a decrease in skeletal area. Exposure to acrylamide in maternal rats during the lactation period disturbed bone mineral density, serum levels of parathyroid hormone, and the expression of skeletal development-related genes in neonates. Exposure to acrylamide in pregnant rats during the pregnancy period decreased the trabecular density and inhibited cartilage formation by delaying the differentiation of osteoblasts and promoting the maturation of osteoclasts in rat embryos. Furthermore, acrylamide intervention downregulated the expression of chondrocyte and osteoblast differentiation-related genes (sox9a, bmp2, col2a1, and runx2), and upregulated the expression of osteoclast marker genes (rankl and mcsf) in zebrafish and rat embryos at different gestational stages. Our results indicated that exposure to acrylamide dysregulated signature gene and protein expression profiles of skeletal development by suppressing the differentiation and maturation of osteoblasts and cartilage matrix and promoting the formation of osteoclasts, and ultimately induced skeletal abnormality in morphology, which brings increasing attention to the intergenerational toxicity of acrylamide via mother-to-child transmission.

Polychlorinated biphenyls (PCBs) in the air are predominantly the less chlorinated congeners. Non-dioxin-like (NDL) low-chlorinated PCBs are more neurotoxic, and cause neurodevelopmental and neurobehavioral alterations in humans. However, the underlying mechanisms for this neurodevelopmental toxicity remain unknown. In the present study, Wistar rats were treated by gavage with PCB52 (1 mg/kg body weight) or corn oil from gestational day 7 to postnatal day 21. Both the body lengths and weights of the suckling rats at birth were significantly decreased by PCB52 treatment, suggesting developmental toxicity. Although no obvious histopathological changes were observed in the brain, using RNA-sequencing, 208 differentially expressed genes (DEGs) were identified in the striatum of PCB52-treated male offspring, while just 13 DEGs were identified in female offspring, suggesting sex-specific effects. Furthermore, using Gene Ontology enrichment analysis, neurodevelopmental processes, neurobehavioral alterations, and neurotransmission changes were enriched from the 208 DEGs in male offspring. Similarly, using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, neuroactive ligand receptor interactions and multiple synapse pathways were enriched in male offspring, implying dysfunction of the neurotransmission system. Reductions in the protein expressions of these ligand receptors were also identified in the striatum, cerebral cortex, and hippocampus using western blotting methods. Taken together, our findings indicate that PCB52 exposure during gestation and lactation results in the abnormal expression of neurotransmission ligand-receptors in male offspring with a sex bias, and that this may contribute to neurodevelopmental toxicity.

Many studies show that bisphenol A (BPA) is widespread in human breast milk. However, the occurrence of other bisphenol analogues (BPs), including bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), in breast milk is still not well known. In this study, breast milk samples were collected from 190 women in Hangzhou, China, with the aims to characterize the occurrence of BPA, BPS, BPF, and BPAF in these samples and to investigate their effects on postnatal growth of infants through breast milk consumption. BPA (mean 2.5 ng/mL, range < LOD–15 ng/mL) was the most abundant BP in breast milk, followed by BPS (0.19 ng/mL, <LOD–1.3 ng/mL) and BPAF (0.092 ng/mL, <LOD–0.58 ng/mL). BPF was not detected in all breast milk samples. We firstly found that breast milk concentrations of BPA were negatively correlated with infant’s weight or length gain rate. Daily intakes (DIs) of BPs via the consumption of breast milk were calculated for infants, and the mean DI values were 531 ng/kg/day, 53 ng/kg/day, and 24 ng/kg/day for BPA, BPS, and BPAF, respectively. Overall, this study firstly demonstrats that the lactation exposure to BPA through breast milk consumption may affect the postnatal growth of infants.

Maternal nicotine exposure during lactation induces liver damage in adult male rats. However, the mechanism in males is unknown and females have not been tested. Here, we determined the liver lipid composition and lipogenic enzymes in male and female offspring at two ages in a model of postnatal nicotine exposure. Osmotic minipumps were implanted in lactating Wistar rat dams at postnatal day (PND) 2 to release 6 mg/kg/day of nicotine (NIC group) or saline (CON group) for 14 days. Offspring received a standard diet from weaning until euthanasia at PND120 (1 pup/litter/sex) or PND180 (2 pups/litter/sex). At PND120, NIC males showed lower plasma triglycerides (TG), steatosis degree 1, higher hepatic cholesterol (CHOL) ester, free fatty acids, monoacylglycerol content as well as acetyl-coa carboxylase-1 (ACC-1) and fatty acid synthase (FAS) protein expression in the liver compared to CON males. At this age, NIC females had preserved hepatocytes architecture, higher plasma CHOL, higher CHOL ester and lower total CHOL content in the liver compared to CON females. At PND180, NIC males showed steatosis degrees 1 and 2, higher TG, lower free fatty acids and total CHOL content in the liver and an increase in ACC-1 hepatic protein expression. NIC females had higher plasma TG and CHOL levels, no change in hepatic morphology, lower CHOL ester and free fatty acids in the liver, which also showed higher total ACC-1 and FAS protein expression. Maternal nicotine exposure induces long-term liver dysfunction, with an alteration in hepatic cytoarchitecture that was aggravated with age in males. Concerning females, despite unchanged hepatic cytoarchitecture, lipid metabolism was compromised, which deserves further attention.

It has been suggested that the toxic effects of cadmium (Cd) may disrupt ovarian and uterine functions in adults. However, Cd exposure during gestation and lactation and its effects on the reproductive development in female offspring is still not clear, and the mechanisms underlying exposure toxicology remain mostly unexplored. To investigate how Cd exposure of female rats (F0) during gestation and lactation affects the reproductive development of their female offspring, we studied the steroidogenesis, folliculogenesis, puberty onset, and litter size of the first (F1) and second (F2) filial generations following F0 female rats which had been exposed to CdCl2. The mechanisms related to the early onset of puberty induced by such exposure in female offspring were explored. Maternal exposure to Cd dramatically increased the biosynthesis of steroid hormones in F1 female offspring by the activation of cAMP/PKA pathway and up-regulated expression of steroidogenesis related proteins such as StAR, CYP11A1, 3β-HSD and CYP19A1. The high levels of steroid hormones contributed to an early puberty onset, promoted the differentiation and maturation of follicles, and led to the proliferation of endometrium that resulted in a uterus weight gain. The increased number of antral follicles eventually caused a big litter size. Despite of being free from additional Cd exposure, the levels of CYP11A1 and CYP19A1 in the ovaries of F2 female rats were also high, which resulted in a high concentration of serum progesterone. These results suggested that hormonal changes induced by exposure to Cd in utero might have a lasting effect beyond the first generation. These findings may help to better understand the origin of female sexual dysfunction in the developmental stages in general.